Effects of danazol on gonadotropin levels in castrated rhesus monkeys.

Danazol is widely used in the management of endometriosis and mammary dysplasia. However, its mechanism of action is still obscure because of the few studies done and the controversial results obtained. Antigonadotropic activity has been postulated by some investigators, whereas others have observed no effect on the gonads. In the present study, three castrated female rhesus monkeys received 400 mg of danazol daily, by gavage for 19 days, while 2 controls received 400 mg of lactose daily. Blood samples were drawn every other day from 2 weeks prior to 3 weeks after the administration of the drug. Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased rapidly and then were maintained until danazol was discontinued. Prompt return to pretreatment levels occurred 1-2 days after the discontinuation of therapy. Prolactin levels were normal during therapy. Luteinizing hormone releasing factor (LH-RF), 100 microgram, administered intravenously during danazol therapy, caused a normal, prompt release of gonadotropins, demonstrating an intact pituitary response. The authors conclude that 1) danazol is a potent antigonadotropic agent, 2) its effect is abolished promptly after discontinuation, and 3) its probable biological action is at the hypothalamic level.     

Low-dose follicular-phase cocaine administration disrupts menstrual and ovarian cyclicity in rhesus monkeys

OBJECTIVE: To evaluate the effects of daily low-dose follicular-phase cocaine administration on menstrual cyclicity, ovulation rates, corpus luteum function, and hormone levels in rhesus monkeys. METHOD: Normally cycling, drug-naive, adult rhesus monkeys were randomized to receive either 1 mg/kg of cocaine (n = 7), 2 mg/kg of cocaine (n = 7), or normal saline (n = 7) daily on cycle days 2 to 14. Daily blood samples were obtained through indwelling catheters for measurement of serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to determine onset of menses. Laparoscopy was performed 2 days after the midcycle estrogen peak to document ovulation. Daily caloric intakes as well as pretreatment and posttreatment weights were recorded. RESULTS: Two of seven monkeys receiving 1 mg/kg per day and two of seven monkeys receiving 2 mg/kg per day of cocaine had timely ovulation and normal menstrual cycle lengths. One monkey receiving the 2-mg/kg dose ovulated on cycle day 24 and had a short luteal phase (7 days) with a mean progesterone level of 2.4 ng/mL. All seven saline-treated control monkeys ovulated normally; the mean cycle length was 29 days and all had adequate luteal phases. The difference in ovulation rates between cocaine-treated and control monkeys was statistically significant (P = .003). There were no differences in basal levels of LH or FSH between treatment groups. There were no significant differences in weight change or caloric intake among groups. One third of the subsequent menstrual cycles in cocaine-treated monkeys were of abnormal duration. CONCLUSION: Daily low-dose follicular-phase cocaine administration disrupts menstrual cyclicity and folliculogenesis. This effect is independent of weight loss, caloric intake, and basal gonadotropin levels. Cocaine exposure may have a persistent effect on menstrual and ovarian cyclicity in some monkeys.     

Induced varicoceles in rhesus monkeys.

Varicoceles were surgically induced unilaterally in seveh rhesus monkeys. Effects of the varicoceles were documented by quantitative and qualitative changes in the semen analysis and testicular biopsies. Testicular temperatures appeared to be higher bilaterally in animals with varicoceles. Testosterone and estradiol levels in the testicular vein were somewhat higher on the experimental side. We found no evidence for adrenal retrograde flow.     

Depot medroxyprogesterone acetate and basal serum prolactin levels in lactating women

OBJECTIVE: To study the effect of depot medroxyprogesterone acetate on basal serum prolactin levels in lactating women. METHODS: We compared basal serum prolactin levels in 25 lactating women after depot medroxyprogesterone acetate injection and in 25 lactating women of similar age who were using a copper T380A intrauterine device (control group). This sample size was required in order to have 95% power to detect a significant difference. Basal prolactin levels were evaluated by time-resolved fluoroimmunoassay three times (6 weeks postpartum and 3 and 6 weeks after beginning either contraceptive method). RESULTS: At 6 weeks postpartum, before beginning either contraceptive method, the mean prolactin levels in the study and control groups were 991.31 and 948.75 mU/L, respectively (P =.850, 95% confidence interval [CI] -407.57, 492.70). Three weeks later, the mean prolactin levels in the study and control groups were 1156.12 and 860.10 mU/L, respectively (P =.116, 95% CI -76.20, 668.26). At the last follow-up, the mean prolactin levels in the study and control groups were 1127.83 and 710.97 mU/L, respectively (P =.026, 95% CI 51.97, 781.73). There were no significant within-group differences at 6 weeks postpartum before contraception and at 6 weeks after beginning contraception in the study and control groups (P >.05, 95% CI -327.99, 243.02 and -46.76, 522.33, respectively). CONCLUSION: Contraception with depot medroxyprogesterone acetate in lactating women produced higher basal prolactin levels than contraception with copper T380A intrauterine device.     

Influence of basal and post-feeding prolactin levels on amenorrhea during breast feeding]

Forty five women, with exclusive breastfeeding were studied, (the objective was) to explore the relationship between: basal plasma prolactin (PRL) levels and post-suckling with the duration of postpartum amenorrhea. Blood samples for measurements of PRL were taken at the third month postpartum, before an episode of suckling and 30 minutes after the suckling was initiated. The average level of basal PRL was 1,033 +/- 113 mIU/L (mean +/- SE). Women who presented long periods of amenorrhea, had an increase of the basal PRL in 632 mIU/L (X), compare to those women who had their menses before 180 days postpartum (p = 0.036) women with longer amenorrhea (p = 0.06). However there were no relationship between the menses at the sixth month postpartum and the increase of post-suckling PRL (delta PRL). In this study it was found that the levels of basal PRL had correlation with the duration of the amenorrhea, in women with exclusive breastfeeding.     

Cell-mediated immunity in vasectomized rhesus monkeys.

Cell-mediated immunity in rhesus monkeys that had been vasectomized for 2, 4, 7, or 11 years was measured by lymphocyte blastogenesis following stimulation with concanavalin A, phytohemagglutinin (PHA), and pokeweed mitogens. Several of the 7- and 11-year vasectomized animals had significantly reduced PHA reactivity when compared with control animals, and the percentage of animals with reduced PHA reactivity increased with time after vasectomy.     

Interceptive activity of azastene in rhesus monkeys.

Azastene is an orally effective "luteolytic" agent in rhesus monkeys. In nonpregnant monkeys it reverses the human chorionic gonadotropin-stimulated increase in progesterone production and delay in the onset of menstruation, and, in inseminated monkeys, it prevents pregnancy if given for 5 days beginning on day 24 of the menstrual cycle. The drug is also effective in terminating pregnancy if given for 5 days beginning on approximately day 26, day 50, or day 80 of gestation. Concurrent progesterone administration prevents the interceptive action of the drug. Although azastene inhibits gonadal and placental progesterone production, it has no effect on cortisol production in monkeys and is devoid of apparent hormonal activity.     

Effects of naloxone infusion on basal and breast-stimulation-induced prolactin secretion in puerperal women

The effects of naloxone infusion on plasma prolactin (PRL) levels and on the PRL response to mechanical breast emptying were investigated in a group of puerperal women, Five, 10, and 20 mg naloxone administered to women on days 2 to 3 of the puerperium produced no significant change in serum PRL. The same dose of naloxone had no significant effect on serum PRL response to mechanical breast stimulation in puerperal women. The results suggest that endogenous opioid peptides are not major modulators of PRL secretion in the puerperium.     

Pulsatile gonadotropin secretion and basal prolactin levels during dopamine D-1 receptor stimulation in normal women.

The effect of the specific dopamine D-1 receptor agonist Fenoldopam on pulsatile gonadotropin secretion and prolactin (PRL) secretion was investigated in normal women. The gonadotropin response to subsequent gonadotropin-releasing-hormone (GnRH) administration was also studied. Eight women received 8-hour infusions of either Fenoldopam (0.5 microgram/kg per minute) (Smith Kline and French, Harrow, United Kingdom) or placebo. After 7 hours of infusion, GnRH was given intravenously. The luteinizing hormone (LH) response to GnRH was significantly higher during Fenoldopam compared with placebo (LH; 13.1 +/- 9.0 versus 9.4 +/- 4.3 IU/L). Basal LH levels, pulse amplitude, and pulse frequency during Fenoldopam infusion were not different from placebo. Prolactin levels increased significantly during Fenoldopam (24 +/- 2 micrograms/L) compared with placebo (16 +/- 2). The results suggest that D-1 receptor stimulation does not affect pulsatile gonadotropin secretion but increases the pituitary responsiveness to GnRH. Additionally, dopamine and Fenoldopam have opposite effects on PRL secretion, the latter increasing PRL levels.     

Effects of opioid antagonism with naltrexone on pulsatile luteinizing hormone secretion in women with hypothalamic amenorrhea in basal conditions and after discontinuation of treatment with pulsatile LHRH.

Although endogenous opioids seem to play an important role in the inhibition of luteinizing hormone releasing hormone (LHRH) secretion in women with hypothalamic amenorrhea, opioid antagonism does not always cause an increase of pituitary luteinizing hormone (LH) secretion. The effect of the long-acting oral opiate antagonist naltrexone on pulsatile LH secretion was studied in eight women with weight loss and exercise-related hypothalamic amenorrhea. LH pulse studies and LHRH tests were performed in basal conditions and after 4 days of naltrexone treatment, 50 mg q.d. Naltrexone caused a slight, but significant increase of LH pulse frequency. Six weeks later, a second experiment was performed. The response to naltrexone was studied after enhancement of the pituitary sensitivity. Patients were pretreated with pulsatile LHRH during 4 days, followed by naltrexone 50 mg q.d. during 4 days. An increased LH response to LHRH, but no response to naltrexone, were seen after discontinuation of pulsatile LHRH. It is concluded that the limited pituitary response to opioid antagonism, observed in weight loss-related forms of hypothalamic amenorrhea, is not caused by pituitary insensitivity to LHRH.     

Testosterone production and metabolism in laboratory-maintained male rhesus monkeys.

Plasma production rates (PR), metabolic clearance rates (MCR) and plasma levels of testosterone were determined in 10 male, laboratory-maintained rhesus monkeys on two occasions out-of-season (April and August) and once in-season (October). Plasma testosterone levels in October were higher than those in April and August. The plasma PR was unchanged in August, but markedly increased in October, as compared to April. The MCR showed a parallel increase betueen August and October. Thus changes in testosterone production and metabolism can be observed between in- and out-of-season male rhesus monkeys, maintained under strict laboratory conditions. These changes must be taken into consideration when the male rhesus minkey is used as an experimental model for human reproductive endocrinology.     

Serum prolactin levels in galactorrhea.

Some patients with galactorrhea will have normal serum prolactin levels but many will have elevated serum prolactin levels. The galactorrhea may be due to drug ingestion, nipple afferent nerve stimulation, nonneoplastic disease or injury, and intracranial tumors. Serum prolactin levels were measured by radioimmunoassay in 17 women with galactorrhea. Levels 5 and 6 times normal values were found in two women who had proved pituitary adenomas. The latter conditions must be strongly considered and functional tests may help in diagnosis prior to enlargement of a prolactin-secreting tumor to the size where changes in the sella are seen on x-ray or visual field changes occur. If galactorrhea persists when no evidence of tumor can be found, the patient must be periodically re-evaluated, as the tumor may have been too small for detection at the time of the previous examination.